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World J Stem Cells. May 26, 2023; 15(5): 400-420
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.400
Different priming strategies improve distinct therapeutic capabilities of mesenchymal stromal/stem cells: Potential implications for their clinical use
Vitale Miceli, Giovanni Zito, Matteo Bulati, Alessia Gallo, Rosalia Busà, Gioacchin Iannolo, Pier Giulio Conaldi
Vitale Miceli, Giovanni Zito, Matteo Bulati, Alessia Gallo, Rosalia Busà, Gioacchin Iannolo, Pier Giulio Conaldi, Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Palermo 90127, Italy
Author contributions: Miceli V collected the literature, prepared illustrative materials, and wrote the original draft; Miceli V, Zito G, Bulati M, Gallo A, Busà R, Iannolo G, and Conaldi PG wrote, reviewed, and edited the draft; Miceli V and Conaldi PG supervised the manuscript; and all authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Vitale Miceli, PhD, Academic Editor, Research Scientist, Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta Specializzazione), Via Tricomi 5, Palermo 90127, Italy.
Received: January 27, 2023
Peer-review started: January 27, 2023
First decision: February 28, 2023
Revised: March 7, 2023
Accepted: April 17, 2023
Article in press: April 17, 2023
Published online: May 26, 2023

Mesenchymal stromal/stem cells (MSCs) have shown significant therapeutic potential, and have therefore been extensively investigated in preclinical studies of regenerative medicine. However, while MSCs have been shown to be safe as a cellular treatment, they have usually been therapeutically ineffective in human diseases. In fact, in many clinical trials it has been shown that MSCs have moderate or poor efficacy. This inefficacy appears to be ascribable primarily to the heterogeneity of MSCs. Recently, specific priming strategies have been used to improve the therapeutic properties of MSCs. In this review, we explore the literature on the principal priming approaches used to enhance the preclinical inefficacy of MSCs. We found that different priming strategies have been used to direct the therapeutic effects of MSCs toward specific pathological processes. Particularly, while hypoxic priming can be used primarily for the treatment of acute diseases, inflammatory cytokines can be used mainly to prime MSCs in order to treat chronic immune-related disorders. The shift in approach from regeneration to inflammation implies, in MSCs, a shift in the production of functional factors that stimulate regenerative or anti-inflammatory pathways. The opportunity to fine-tune the therapeutic properties of MSCs through different priming strategies could conceivably pave the way for optimizing their therapeutic potential.

Keywords: Mesenchymal stromal/stem cells, Mesenchymal stromal/stem cell therapeutic properties, Mesenchymal stromal/stem cell paracrine effects, Mesenchymal stromal/stem cell priming, Pro-inflammatory priming, Hypoxic priming, 3D culture priming

Core Tip: Mesenchymal stromal/stem cells (MSCs) have demonstrated promising therapeutic results in the field of regenerative medicine. However, due to their heterogeneity, the application of MSCs in clinical trials has shown moderate or poor efficacy. Here, we review data on the principal priming approaches for enhancing the therapeutic potential of MSCs. We found that different priming strategies can modify MSC properties and, in this case some therapeutic effects on different disease models can be obtained in relation to dose and/or combination of the priming factors used. The production of priming type-specific functional factors in MSCs could pave the way toward implementing new MSC-based therapies.